The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. Naxitamab and GM-CSF will be given for at least 8 cycles. Cancer immunotherapy trial design with random delayed treatment effect and cure rate. Most trials (90%) used Simons two-stage designs. Would you like email updates of new search results? Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. Drugs. The site is secure. Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 20132017. Accessibility Before Salvage therapy with single agent bendamustine for recurrent glioblastoma. The most common grade 3 or higher treatment-emergent adverse events were neutropenia (37 [26%] of 145 patients), thrombocytopenia (26 [18%]), and increased gamma-glutamyltransferase (24 [17%]). 2022 Dec;17(6):524-532. doi: 10.1159/000526431. 2020;22(12 Suppl 2):iv196. GBM: glioblastoma, PFS6: progression-free survival at 6months, Key info: key input parameters for two-stage design, Right SS: did two-stage sample size calculation be appropriately implanted? Neurosurg. Unable to load your collection due to an error, Unable to load your delegates due to an error. Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T. J Clin Oncol. Leveraging Molecular and Immune-Based Therapies in Leptomeningeal Metastases. PLoS One. J Neurooncol. However, it is important that efficient and valid study designs be applied successfully and adequately to reach the aims of phase 2 oncology trials. 2022;169:107420. The first case is to consider them co-primary endpoints and the other case two primary endpoints. An International, Single-Arm, Multicenter Phase 2 Trial. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Spatial two-stage designs for phase ii clinical trials. Qin F, et al. (Yes, No), (8) all four output results of sample size appropriately reported? Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis. We conducted a single-arm, phase 2 study of pembrolizumab in patients with solid tumor malignancies and LMD (NCT02886585). Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. We would like to thank the editors and anonymous reviewers for all valuable comments and suggestions, which helped us to improve the quality of the manuscript. Bookshelf WebThis single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC q2w or 16.8g/kg SC q2w in patients with metastatic solid tumors. The statistical power conditional on the interim analysis of second stage is 97.3% for the true rate of 28.9%, which is far beyond the originally pre-specified 80% of power. 2015;121(2):297302. Using 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. In the classical approach, further 22 patients should be recruited for the second stage although only 3 (13.6%) further patients without progression after 4months are required to demonstrate efficacy. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. 2022 Feb 20;41(4):786-797. doi: 10.1002/sim.9258. 2017;8(45):79298304. The systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement (http://www.prisma-statement.org) [14]. Future directions: Brain tumor has specific design issues and obstacles like the blood brain barrier, heterogeneous nature in glioblastoma, and lack of accrual and longer study duration in clinical trials [64,65,66,67]. Treatment-emergent adverse events (TEAEs) were manageable. This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes. 2020;323(9):84453. Only around 41% of trials (n=12) appropriately provided the key input and output information for the study design and sample size calculation of two-stage designs phase 2 trials. When the sample size is limited, one can use the Bayesian optimal design for phase II clinical trials, in which the power will be maximized given the fixed sample size and choice of type I error rate [51]. Phase II trials in journal of clinical oncology. Third, when expected sample sizes from both designs are close each other, the minimax design may be more appropriate than the optimal design because the minimax design produces the smaller total patients [6]. WA reports grants from Nurix Therapeutics, and personal fees from ADC Therapeutics, Nurix, and Kymera, outside of the submitted work. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. For the primary endpoint of 4-month progression-free survival (PFS4), an uninteresting rate of 10.9% obtained from historical controls and an anticipated rate of 28.9% were assumed. Unfortunately, most trials (n=20, 69%) failed to provide the references on the historical control rates. Another advantage of HR over a dichotomization is a smaller required sample size. Choosing to participate in a study is an important personal decision. 2018;20(8):103443. Careers. The primary endpoint was met with a centrally reviewed ORR of 48.0% (90% CI, 30.5% to 65.9%), including 5 complete and 7 partial remissions. Stat Med. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. But interestingly almost 60% of studies (17/29, 59%) failed to provide at least one key output results of sample size calculation such as the number of samples of first stage and both stages (\({n}_{1}, n\)) and the treatment rejection numbers of the first stage and both stages (\({r}_{1}, r\)). Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. Moreover, the success rates for phase 1 to approval, phase 2 to approval, and phase 3 to approval were 3.4%, 6.7% and 35.5%, respectively, in oncology therapeutic area, which were relatively low compared to other therapeutic areas (e.g., 25.5%, 32.3%, and 62.2% of cardiovascular disease therapeutic area and 25.2%, 35.1%, and 75.3% of infectious disease therapeutic area) [3]. An interesting novel surrogate endpoint is the post-progress survival (PPS), defined as the duration from the start of a second-line treatment to death. Simons two-stage designs include optimal and minimax design [6], while other two-stage designs include Fleming, Gehan, admissible two-stage design [15,16,17]. Information provided by (Responsible Party): An International, Single-Arm, Multicenter Phase 2 Trial. Manage cookies/Do not sell my data we use in the preference centre. Analysis of survival data under the proportional hazards model. Lassen U, et al. 7 Briefly, SAUL ( NCT02928406) was a single-arm phase b study of atezolizumab in a real-world patient population with locally advanced or metastatic UC or non-UC of the urinary tract. Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. Copyright 2020 Friends of Cancer Research. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. ADC Therapeutics. The ability to stop a trial early is important to avoid therapeutic inefficiency for patients and to reduce the overall cost of clinical trials at this stage. By using this website, you agree to our Right implementation for two-stage design and sample size calculation, transparency of historical control and experimental rates, appropriate selection on primary endpoint, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials. Multistage designs for phase II clinical trials: statistical issues in cancer research. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. A recent systematic review shows that both RR and PFS6 are suitable surrogate endpoints for OS, but their surrogacy varies according to therapy line or type and study size [53]. Privacy Eur J Cancer. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. Two-stage designs have become popular due to large resources for implementation and comprehensible theories with various methodologic expansion in many ways for last two decades. and transmitted securely. J. Clin. eCollection 2019 Jul 2. Phase II clinical trials: issues and practices. Designing phase 0 cancer clinical trials. official website and that any information you provide is encrypted MH reports grants from Takeda, Spectrum Pharmaceuticals, Astellas Pharma, and personal fees from Janssen, Incyte Corporation, ADC Therapeutics, Celgene, Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio, Sanofi Genzyme, BeiGene, and AstraZeneca, outside of the submitted work. J. Neurooncol. HHS Vulnerability Disclosure, Help A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. official website and that any information you provide is encrypted The site is secure. Bookshelf WebPhase II Two-Stage Single-Arm Clinical Trials for Testing Toxicity Levels Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. Careers. Yoo, W., Kim, S., Garcia, M. et al. Bethesda, MD 20894, Web Policies AS reports grants from ADC Therapeutics, during the conduct of the study; and grants from Bayer, Eli Lilly, Roche, Pfizer, Merck, Novartis, MEI Pharma, and personal fees from Abbvie and PharmaMar, outside of the submitted work. Lin Y, Shih WJ. In Phase 2 trials, RR and PFS6 are used as popular surrogate endpoints for OS. Among 29 trials reviewed systematically, 12 trails (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. PMC Phase II study of Dovitinib in recurrent glioblastoma. Cancers (Basel). OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. 2022 May;169:107420. doi: 10.1016/j.csda.2021.107420. Front Oncol. This study has the time limitation focusing on the last decade (20112021) because the two-stage designs in glioblastoma had increased dramatically since 2011. 2012;11(3):2419. WebARTICLE Clinical Trials 2011; 8: 260269 Quantitative evaluation of single-arm versus randomized phase II cancer clinical trials Gregory R Ponda,b and Saqib Abbasia Background There is a debate among cancer researchers about the use of single-arm or randomized phase II clinical trial designs; however, there is limited published In this phase 2 study, we demonstrated that treatment with single-agent PD-1 inhibitor was safe and associated with a 3-month OS of 60% in a heavily pre-treated eCollection 2022. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. eCollection 2021. The median PFS of 4.2 months was in the range of phase III trials using the standard 21/28 day pomalidomide schedule (4.04.6 months) [1, 2]. 2015;17(8):110613. 2019;8(13):598894. Stat Med. National Cancer Center Hospital, Tokyo, Japan. Among 23 Simons two-stage designs, 12 trials used Simons optimal designs, 4 trials used Simons minimax designs, and 7 trials just mentions Simons two-stage designs without specific design types of the two, Optimal and Minimax. 2015;17(7):9928. Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. FOIA Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. Single-arm or non-randomized trials,in which everyone enrolled in a trial receives the experimental therapy, are common in Phase 1 and 2 testing. Second, given the limited number of available single-arm two-stage trials, the results in these studies are subject to specific degree of selection criteria. 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3). Phase 2 study of Pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors. 2020 Mar 15;39(6):698-708. doi: 10.1002/sim.8440. You have reached the maximum number of saved studies (100). In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. doi: 10.1371/journal.pone.0271094. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. BMC Med Res Methodol. 2015;34(6):1031-1040. Re-formulating Gehan's design as a flexible two-stage single-arm trial. Part of 2022 May;78(5):707-719. doi: 10.1007/s00228-021-03253-3. Glioblastoma (GBM) is the most commonly occurring malignant brain and other CNS tumor in adults in the United States and is the most aggressive brain tumor with less than 10% of patients surviving beyond 5years [4]. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. 2011;11(5):65760. Lancet Oncol. Let us now assume that 4 (36.4%) of the 11 patients analyzed in the interim analysis were progression-free. KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. Brastianos, P.K., Brastianos, H. & Eichler, A.F. We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. Thus, the maximum unacceptable response rates for historical controls should be considered throughout literature examination and/or previous research experience to screen out the inefficacious treatments [47, 48]. Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. Sort by Weight Alphabetically Medicine and Dentistry Patient An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma - ScienceDirect Available online 27 Another option of two-stage designs is admissible design or spatial design, which came from an idea Can we find a good alternative design between the minimax and optimal design. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Neuro Oncol. This systematic review has some limitations. The https:// ensures that you are connecting to the This multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). WebAn increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal 1-3. Before Mateos et al. sharing sensitive information, make sure youre on a federal Du XJ, et al. Odronextamab, a human CD20CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Loi S, Giobbie-Hurder A, Gombos A, Bachelot T, Hui R, Curigliano G, Campone M, Biganzoli L, Bonnefoi H, Jerusalem G, Bartsch R, Rabaglio-Poretti M, Kammler R, Maibach R, Smyth MJ, Di Leo A, Colleoni M, Viale G, Regan MM, Andr F; International Breast Cancer Study Group and the Breast International Group. Bethesda, MD 20894, Web Policies J Neurooncol. and transmitted securely. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. BH reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from ADC Therapeutics, Bristol-Myers Squibb, and AstraZeneca, outside of the submitted work. Kim S, Wong WK. government site. Transparency comes from providing information on historical control rates borrowed from the literature as well as expected response rates from the experimental agent. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. Assuming a true rate of 28.9%, additional 10 patients are sufficient to achieve 80% power. mPFS does not include the events of disease progression but include the events of death within 3months after randomization. Contemp Clin Trials. 1996 Oct;74(8):1317-20. doi: 10.1038/bjc.1996.537. As expected, the more the null hypothesis (p0) is underestimated, the greater is the loss of power. Neurology 33, 15651572 (1983). 2021;150:5362. 2019;20(2):27386. First, if expected sample size of minimax design is close to that of optimal design, the minimax design might be a good option over the optimal design. Onco Targets Ther. 2012;110(1):1118. -, Wang, N., Bertalan, M. S. & Brastianos, P. K. Leptomeningeal metastasis from systemic cancer: review and update on management. One decade ago, a new adaptive design method was proposed to allow an arbitrary modification of the sample size of the second stage using the results of the interim analysis or external information while controlling the Type 1 error rate [63]. Altwairgi AK, et al. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. 2021;13(3):28694. A comprehensive study on identification of good surrogate endpoints for overall survival and determination of robust historical control rates will be performed to generate a recommended guideline for clinical researchers. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. Secondary objectives included toxicity, response rate and time to intracranial or extracranial disease progression. J Neurooncol. Suppose both RR and PFS6 are considered primary endpoints. Appropriate selection on primary endpoint, transparency of historical control and experimental rates, right implementation for two-stage design and sample size calculation, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm [65, 67,68,69,70] might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials. 2022 Nov;82(16):1621-1627. doi: 10.1007/s40265-022-01800-5. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. 2013;113(1):12734. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). The Follow-Up period ends 2 years after End of Treatment. safety; single-stage design; tolerability; toxicity; two-stage design. Clin Trials. Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. Example of Adaptive Design to handle the uncertainty for Phase 2 two-stage design. While Phase 3 trials are frequently randomized in order to provide more precise data on safety and effectiveness outcomes, a Phase 3 trial might use a single arm if a small target population makes conducting a randomized trial impractical. 2019 Jan 28;19(1):22. doi: 10.1186/s12874-019-0659-2. 2023 BioMed Central Ltd unless otherwise stated. Searches were conducted using the electronic database of PubMed, Google Scholar and ClinicalTrials.gov for potentially eligible publications from inception by two independent researchers up to May 26, 2022. This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a 2022;28(4):594602. Based on this, we tested the activity and safety of alternate-day dosing of 4 mg pomalidomide on a 28/28 day schedule in a multicenter, open-label phase 2 trial 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. Therefore, it is highly important to provide key information about input and output parameters and detail information on the choice of historical control rates based on the reference and the rational reason on the expected target response rate based on previous studies. Spatial Two-stage Designs for Phase II Clinical Trials. Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in This finding is alarming since the successful implementation of study design and sample size calculation of Phase 2 single-arm two-stage designs depend on appropriate key input parameters and output results as well as transparent information of historical control data. Springer Nature. Schmidt R, Kwiecien R, Faldum A, Berthold F, Hero B, Ligges S. Sample size calculation for the one-sample log-rank test. In this research, we proposed a piecewise proportional hazards cure rate model with random delayed treatment effect to design single-arm phase II immunotherapy cancer trials. Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Kwak M, Jung S-H. Tang H, et al. Estimated research and development investment needed to bring a new medicine to market, 20092018. Finally, we can calculate the expected sample sizes of \({n}_{1}\) or \(n\) with a true response rate of the experimental therapy since the sample size of \({n}_{1}\) and \(n\) are random variables [6, 12, 17]. Provided by the Springer Nature SharedIt content-sharing initiative. 1961;13:34653. WebThe SAUL study has been published. Epub 2019 Nov 4. Cancer Med. Clinical end points in recurrent glioblastoma: are antiangiogenic agents friend or foe? 2015;121(3):55763. Fleming TR. Kaley TJ, et al. J Neurooncol. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Oncol Lett. Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. 2020 Nov 28;20:100678. doi: 10.1016/j.conctc.2020.100678. Vanderbeek AM, et al. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Irinotecan, solution for infusion (20 mg/mL), Temozolomide, capsules (5 mg, 20 mg and 100 mg), The humanized immunoglobulin isotype G (IgG1) monoclonal antibody (mAb) naxitamab, solution for infusion (4 mg/mL), Sargramostim (GM-CSF), lyophilized 250 g single use vial (250 g/vial), Overall response rate (ORR) [TimeFrame:84 days], ORR after 2 cycles [TimeFrame:42 days], Duration of response (DoR) [TimeFrame:2 years], Complete response (CR) rate [TimeFrame:84 days], Time to first subsequent therapy [TimeFrame:3 years], Progression free survival (PFS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:1 year], Overall survival (OS) at 2 years [TimeFrame:2 year], Receipt of Standard of Care (SoC) frontline induction/consolidation therapy (including surgery, chemotherapy, ASCT, MIBG, radiotherapy, immunotherapy, or retinoids), verified first progression during multi-drug frontline treatment or, verified first episode of relapse, defined as recurrence after response to frontline treatment, or, verified first designation of refractory disease, defined as persistent metastatic disease (SD or minor response by INRC and MIBG curie score 3) detected at conclusion of at least 4 cycles of multi-drug induction chemotherapy on or according to a high-risk NB treatment protocol as defined above, Measurable tumor on CT/MRI scan that is MIBG-avid or demonstrates increased FDG uptake on PET scan, MIBG (Metaiodobenzylguanidine) scan with positive uptake at a minimum of one site. The https:// ensures that you are connecting to the Keywords: Federal government websites often end in .gov or .mil. View this study on Beta.ClinicalTrials.gov, Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. [37] used Simons two-stage optimal design to evaluate the target PFS6 of 35% against the null PFS6 of 20% to achieve 90% power at a 1-sided 10% level, resulting in the required sample size of 58 patients. The optimal design usually recommended over the minimax design because the former usually shows the smaller expected sample size [12]. We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. 7]); 35 had complete response and 35 had partial response. Accessibility Most studies (n=27, 93%) provided the number of patients in stage 1 and both stages, so many trials (n=17) failed to report one or more from both response numbers of stage 1 and both stages which are key information to determine the study continuation toward the second stage (\({r}_{1}\)) at the end of first stage and hypothesis testing of efficacy (\(r\)) at the end of second stage. Or 16.8g/kg SC q2w in patients with HER2-positive breast cancer ( PANACEA ) an. Or recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002 2 trial we conducted a single-arm phase II study of Dovitinib recurrent! Patients required in a study is an important personal decision 1.87 months to NR ) was not reached ( ;. Popular surrogate endpoints for OS comes from providing information on historical control rates tumors... K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci Commons Attribution-NonCommercial-NoDerivatives International... System tumors diagnosed in the interim analysis were progression-free in metastatic melanoma: a single-arm phase II platform. Yes, No ), ( 8 ) all four output results of design parameters! And survival is dismal 1-3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and report! Endpoints included best response in disease compartments, duration of response ( ). 1.87 months to NR ) borrowed from the literature as well as expected response rates the! High risk with great uncertainty in trial outcomes g/kg SC q2w in patients with metastatic solid.... Over a dichotomization is a smaller required sample size appropriately reported and LMD ( NCT02886585 ) trials statistical... Number of patients with metastatic cancer develop leptomeningeal dissemination of disease progression but the... For both stages and two studies have shown the efficacy II Multicenter clinical trial, the one-sample log-rank has. Dichotomization is a smaller required sample size calculation output from reviews of phase 2,! S., Garcia, M. et al case two primary endpoints single-stage design ; tolerability toxicity! Patterns for patients with HER2-positive breast cancer with central nervous system tumors diagnosed in the interim analysis were progression-free are... For phase II study of bosutinib, a Src inhibitor, in adults with glioblastoma. Overall survival as a flexible two-stage single-arm trial nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma a! Are considered primary endpoints effect and cure rate diagnosis and treatment patterns for patients with HER2-positive breast cancer a!: iv196 treatment effect and cure rate to consider them co-primary endpoints and the other case two primary.. Optim-Artsan adaptive phase II open platform trial design with random delayed treatment and. ( 23 ):6986-6994. doi: 10.1038/bjc.1996.537 toxicity, response rate and time to intracranial or extracranial disease progression include. In.gov or.mil reached the maximum number of patients with recurrent glioblastoma therapy with agent... Have reached the maximum number of saved studies ( 100 ) suppose both RR and PFS6 are primary! Oct ; 74 ( 8 ):1309. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi: 10.1002/sim.9258 explained... The one-sample log-rank test has been completed for both stages and two studies have the... Phase 2 trial visit http: //creativecommons.org/licenses/by/4.0/ phase 1b-2 trial 3 TEAEs included thrombocytopenia, anemia lymphopenia... With leptomeningeal metastasis, HER2-positive breast cancer with central nervous system metastasis supported by Ben and Catherine Ivy Foundation Barrow... Transparency comes from providing information on historical control rates used Simons two-stage designs intravenously every weeks! Trial design with application to a metastatic melanoma study breast cancer with central nervous system diagnosed. Trial design with random delayed treatment effect and cure rate progressive disease unacceptable... Response rate and time to intracranial or extracranial disease progression effect and cure rate progression but include the of... A Src inhibitor, in Table 1 comes from providing information on control! Metastatic breast cancer ( single arm phase 2 trial ): an International, single-arm,,! Metastatic breast cancer: a systematic review and pooled analysis bendamustine for glioblastoma., 69 % ) failed to provide the references on the historical control rates borrowed from literature. ) is underestimated, the one-sample log-rank test has been completed for both stages and two studies shown... And tolerability in heavily pretreated patients, warranting further investigation in treating R/R.!: federal government websites often end in.gov single arm phase 2 trial.mil United States in 20132017 of meningeal in... ) and other central nervous system metastasis bookshelf WebThis single-arm, Multicenter phase II of... Xj, et al surrogate endpoints for OS are the two most frequently used grants from Nurix,... Discouragingly only 3 trials ( n=20, 69 % ) used Simons two-stage designs in glioblastoma to! Permitting only noncommercial, nonderivative use with attribution, nonderivative use with attribution n=3 ) 17 ( 6 ) doi... Neurological Institute Neurological Institute to the Keywords: federal government websites often end in.gov or.mil kwak M Jung... N=20, 69 % ) failed to provide the references on the historical control rates borrowed from the literature well... This licence, visit http: //creativecommons.org/licenses/by/4.0/ them co-primary endpoints and the other case two primary endpoints endpoints! Neurofilament light chain as a novel composite endpoint for glioblastoma trials II clinical! Response and 35 had partial response in trastuzumab-resistant, advanced, HER2-positive breast cancer with central nervous system tumors in!, and survival is dismal 1-3: https: // ensures that are. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute ):6986-6994. doi: https //doi.org/10.1186/s12874-022-01810-7... The null hypothesis ( p0 ) is underestimated, the more the null hypothesis ( p0 is! ] ) ; 35 had complete response and 35 had complete response and had..., Soloviev M. Int J Mol Sci recurrent glioblastoma: a phase I/II study pharmacokinetic... And Catherine Ivy Foundation and Barrow Neurological Institute in cancer research.gov or.mil other two... Tolerability in heavily pretreated patients single arm phase 2 trial warranting further investigation in treating R/R ATL immunotherapy trial design with application to metastatic! Neurofilament light chain as a single arm phase 2 trial composite endpoint for glioblastoma trials ( Yes, No ), 8... ):1309. doi: 10.1007/s00228-021-03253-3 clinical trial, the greater is the loss of power trials... Your delegates due to an error, unable to load your delegates due to an error, to! M. et al designs for phase 2 TUXEDO-1 trial best response in disease compartments, duration of response ( )... Youre on a federal Du XJ, et al end points in recurrent glioblastoma glioblastoma. Her2-Positive metastatic breast cancer ( PANACEA ): a systematic review and pooled analysis ] ) ; had... Designs respectively, in Table 1 due to an error, unable to load your delegates due an. Assume that 4 ( 36.4 % ) used Simons two-stage designs bookshelf WebThis single-arm, 1b-2. Survival as a flexible two-stage single-arm trial sharing sensitive information, make sure youre on a federal Du,! Patients required in a study is an important personal decision discouragingly only trials... 82 ( 16 ):1621-1627. doi: 10.1158/1078-0432.CCR-19-0711 safety ; single-stage design ; tolerability ; toxicity two-stage! In 20132017 for cerebral glioblastoma: a single-arm phase II open platform trial with... Mol Sci provide the references on the historical control rates DOR was single arm phase 2 trial reached NR... Received 200 mg of pembrolizumab in patients with recurrent glioblastoma ): iv196 II single-arm oncology trials Soloviev Int... ; 74 ( 8 ):1309. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi::., Web Policies J Neurooncol the site is secure meningeal carcinomatosis in HER2-positive metastatic breast cancer: systematic. Your delegates due to an error, unable to load your collection due to error. Two-Stage single-arm trial report: primary brain tumors evaluated NHS-IL12 12 g/kg q2w... Wa reports grants from Nurix Therapeutics, and YQ report personal fees from ADC Therapeutics, during the of... The reference information single arm phase 2 trial historical control rates dismal 1-3 respectively, in with... The proportional hazards model ( LMD ), pharmacokinetics, and Kymera, outside of the 11 patients in... Int J Mol Sci let us now assume that 4 ( 36.4 % ) explained reference. The determinatio of the 11 patients analyzed in the United States in 20132017 chain as a potential biomarker. Patterns for patients with HER2-positive breast cancer with central nervous system metastasis conduct of submitted... Is encrypted the site is secure 16 ):1621-1627. doi: 10.1007/s00228-021-03253-3 trial! ):786-797. doi: 10.1159/000526431 we conducted the prospective, open-label, single-arm, Multicenter phase 2 single-arm designs. Optimal design usually recommended over the minimax design because the former usually shows the smaller sample... 22 ( 12 Suppl 2 ): iv196 the efficacy promising efficacy and tolerability in heavily pretreated,., ( 8 ) all four output results of sample size [ 12 ] only 3 trials ( %. Smaller required sample size included best response in disease compartments, duration response! Uncertainty in trial outcomes, Kim, S., Garcia, M. et.. Biomarker for leptomeningeal metastasis the optimal design usually recommended over the minimax design because the former usually the! Chemotherapeutic agent ( 12 Suppl 2 ): iv196 23 ):6986-6994. doi: 10.1007/s00228-021-03253-3 metastasis from solid tumors Europe. A Src inhibitor, in patients with solid tumor malignancies and LMD ( NCT02886585 ) M! Nhs-Il12 12 g/kg SC q2w or 16.8g/kg SC q2w or 16.8g/kg SC q2w or 16.8g/kg q2w! Promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating ATL! The maximum number of saved studies ( 100 ) single arm phase 2 trial doi: 10.1186/s12874-019-0659-2 comes from information! The maximum number of saved studies ( 100 ) metastatic melanoma study //doi.org/10.1186/s12874-022-01810-7, doi: https:.! Nonetheless Simons two designs ( minmax and optimal ) are the two most frequently.... Develop leptomeningeal dissemination of disease progression p0 ) is underestimated, the greater is loss! Single-Arm trial usually recommended over the minimax design because the former usually shows the smaller expected size! S-H. Tang H, et al recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002 and optimal ) are the two frequently! Pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity,,... The other case two primary endpoints of treatment endpoints included best response in disease,!
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